Rationale and Design of a Multicenter Trial on Exploratory Analysis of the Effects of Advance Care Planning Guided by the Prediction Program of Heart Failure Prognosis on Quality of Life in Patients With Heart Failure　- ACQUAINT-Trial.

Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. Methods and Results: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF.

Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The impact of quantitative pathological findings derived from endomyocardial biopsies (EMB) on clinical prognosis in patients with hypertrophic cardiomyopathy (HCM) remains unclear. METHODS: We retrospectively studied 55 consecutive HCM patients who underwent EMB. We quantified the collagen area fraction (CAF), the cardiomyocyte diameter, the nuclear area and circularity, and the number of myocardial infiltrating CD3+ cells using EMB samples by image analyzing software. The primary clinical endpoint was defined as a composite including cardiovascular death, admission due to heart failure and ventricular arrhythmia. RESULTS: During the median follow-up of 37.2 months, the primary endpoint was found in 12 patients. No significant difference in the risk score of 5-year sudden cardiac death was observed between the event-occurrence group and the event-free group. In the multivariable Cox proportional-hazard analysis, CAF [hazard ratio (HR) per 10% increase: 1.555, 95% CI: 1.014-2.367, p = 0.044] and the number of infiltrating CD3+ cells (HR per 10% increase: 1.231, 95% CI: 1.011-1.453, p = 0.041) were the independent predictors of the primary endpoint, while the myocardial diameter and the nuclear irregularity had no significant prognostic impact. Kaplan-Meier survival curves demonstrated that patients with both higher CAF and higher number of CD3+ cells had the worst prognosis (log-rank, P < 0.001). CONCLUSIONS: The higher CAF and the higher number of infiltrating CD3+ cells quantified using EMB samples were the independent predictors of poor clinical outcomes in patients with HCM. Cardiomyocyte diameter and nuclear irregularity did not significantly impact the clinical prognosis.

Reclassification of Heart Failure with Preserved Ejection Fraction Following Cardiac Sympathetic Nervous System Activation: A New Cutoff Value of 58.

Heart failure (HF) with preserved left ventricular ejection fraction (LVEF) is a heterogeneous syndrome. An LVEF of 50% is widely used to categorize patients with HF; however, this is controversial. Previously, we have reported that patients with an LVEF of ≥ 58% have good prognoses. Further, cardiac sympathetic nervous system (SNS) activation is a feature of HF. In this retrospective, observational study, the cardiac SNS activity of HF patients (n = 63, age: 78.4 ± 9.6 years; male 49.2%) with LVEF ≥ 58% (n = 15) and LVEF < 58% (n = 48) were compared using 123I-metaiodobenzylguanidine scintigraphy. During the follow-up period (median, 3.0 years), 18 all-cause deaths occurred. The delayed heart/mediastinum (H/M) ratio was significantly higher in the LVEF ≥ 58% group than in the LVEF < 58% group (2.1 ± 0.3 vs. 1.7 ± 0.4, p = 0.004), and all-cause mortality was significantly lower in patients in the former than those in the latter group (log-rank, p = 0.04). However, when these patients were divided into LVEF ≥ 50% (n = 22) and LVEF < 50% (n = 41) groups, no significant differences were found in the delayed H/M ratio, and the all-cause mortality did not differ between the groups (log-rank, p = 0.09). In conclusion, an LVEF of 58% is suitable for reclassifying patients with HF according to cardiac SNS activity.

A case of an elderly female who developed subacute pleuropericarditis following BNT162b2 mRNA COVID-19 vaccination.

Despite the established safety of BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, some rare but serious complications have been previously reported. Here, we report a rare case of an elderly female who developed subacute pleuropericarditis after the vaccination. An 88-year-old female experienced weight gain and dyspnea three days after the second dose of BNT162b2 vaccination, and one month later, presented to our hospital due to the exacerbation of the symptoms. Computed tomography showed remarkable pericardial and bilateral pleural effusions, and transthoracic echocardiogram visualized collapse signs of right and left atrium which indicates pre-tamponade. Percutaneous drainages of pericardial and pleural effusions stabilized her vital condition and revealed that all of them were exudative, indicating the presence of pleuropericarditis. Finally, we diagnosed this case as COVID-19 vaccine-associated pleuropericarditis because there were no signs of bacterial/viral infection or any other relevant causes except for the vaccination. When the pericardial and pleural effusions are concurrently found after COVID-19 vaccination, vaccine-associated pleuropericarditis should be considered as a differential diagnosis. The aggressive drainage of pericardial and pleural effusions could be helpful not only for diagnosis but also for treatment in the clinical management of COVID-19 vaccine-associated pleuropericarditis. Learning objective: Although the safety and efficacy of BNT162b2 have been widely accepted, it is clinically important to know the potential risk of side effects. When the pericardial and pleural effusions are concurrently found after the vaccination, coronavirus disease 2019 vaccine-associated pleuropericarditis should be considered as a differential diagnosis.

Ventricular Sigmoid Septum as a Risk Factor for Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction in Patients With Malignant Lymphoma.

Background: Identifying risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) is essential for the early detection and prompt initiation of medial therapy for CTRCD. No study has investigated whether the sigmoid septum is a risk factor for anthracycline-induced CTRCD. Methods and Results: We enrolled 167 patients with malignant lymphoma who received a CHOP-like regimen from January 2008 to December 2017 and underwent both baseline and follow-up echocardiography. Patients with left ventricular ejection fraction (LVEF) ≤50% were excluded. CTRCD was defined as a ≥10% decline in LVEF and LVEF <50% after chemotherapy. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was measured to quantify the sigmoid septum. CTRCD was observed in 36 patients (22%). Mean LVEF and global longitudinal strain (GLS) were lower, left ventricular mass index was higher, and ASA was smaller in patients with CTRCD. In a multivariable Cox proportional hazard analysis, GLS (hazard ratio [HR] per 1% decrease 1.20; 95% confidence interval [CI] 1.07-1.35) and ASA (HR per 1° increase 0.97; 95% CI 0.95-0.99) were identified as independent determinants of CTRCD. An integrated discrimination improvement evaluation confirmed the significant incremental value of ASA for developing CTRCD. Conclusions: Smaller ASA was an independent risk factor and had significant incremental value for CTRCD in patients with malignant lymphoma who received the CHOP-like regimen.

Multimorbidity, polypharmacy, and mortality in older patients with pacemakers.

BACKGROUND: The prevalence of multimorbidity and polypharmacy and its association with all-cause mortality in older patients with pacemakers are largely unknown. We aimed to clarify the prevalence of multimorbidity and polypharmacy, and its association with all-cause mortality in patients ≥75 years of age with pacemakers. METHODS: We retrospectively investigated 256 patients aged ≥75 years (mean age 84.0 ± 5.3 years; 45.7% male) with newly implanted pacemakers. The study endpoint was all-cause mortality ("with events"). Multimorbidity was defined as a Charlson Comorbidity Index ≥3. Polypharmacy was defined as the use of ≥5 medications. RESULTS: During the follow-up period (median, 3.1 years), 60 all-cause deaths were reported. The Charlson Comorbidity Index (2.9 ± 1.9 vs. 1.7 ± 1.7, p < .001) and prevalence of multimorbidity (56.7% vs. 26.0%, p < .001) were significantly higher in deceased patients than in survivors. The number of drugs (6.9 ± 3.0 vs. 5.9 ± 3.3, p = .03) and the prevalence of polypharmacy (78.3% vs. 63.8%, p = .04) were significantly higher in patients with events than in those without events. The event-free survival rate was significantly higher among patients without multimorbidity than in those with multimorbidity (log-rank, p < .001), and was also significantly higher among patients without polypharmacy than in those with polypharmacy (log-rank, p < .001). Multimorbidity (hazard ratio [HR]: 3.21; 95% confidence interval [CI]: 1.85-5.58; p < .001) and polypharmacy (HR: 1.97; 95% CI: 1.03-3.77; p = .04) were independent predictors of all-cause mortality. CONCLUSIONS: Multimorbidity and its associated polypharmacy, which are common in the older population, are prevalent in patients with pacemakers and are independent predictors of poor prognosis.

Unusual interventional treatment of spontaneous coronary artery dissection without stent implantation: a case series.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a unique cause of myocardial infarction, and optimal treatment should be selected according to the ischaemic condition. Patients with ongoing ischaemia or haemodynamic instability may require revascularization. Cutting balloon (CB) angioplasty has been acknowledged as an option for revascularization. However, few observations of the coronary artery conditions after CB angioplasty in SCAD patients have been reported. Here, we demonstrate two cases in which we evaluated the angiographic morphology of targeted coronary arteries in the chronic phase after CB angioplasty. CASE SUMMARY: Patient 1 was a 46-year-old woman who presented at our hospital with chest pain. Electrocardiography suggested acute coronary syndrome and coronary angiography was performed. The coronary angiography and intravascular ultrasound (IVUS) examinations revealed SCAD in the left anterior descending artery (LAD). Revascularization with CB angioplasty was successful. Follow-up coronary angiography 15 months after the angioplasty showed no visible stenosis in the LAD. Accordingly, the patient no longer needed to antiplatelet therapy. Patient 2 was a 50-year-old woman who was transported to our hospital for ventricular tachycardia. Coronary angiography and IVUS revealed SCAD in the right coronary artery. Coronary flow was restored by CB angioplasty. Follow-up contrast-enhanced computed tomography angiography 36 months after angioplasty showed a healed appearance. Thus, she was able to discontinue antiplatelet therapy. DISCUSSION: Cutting balloon angioplasty may be a possible method to treat SCAD.

Transmission Rate of Remote Monitoring and Mortality in Patients With Pacemaker.

Background: Remote monitoring of cardiac implantable electronic devices improves clinical outcomes, but data on the association between the transmission rate (TR) of the remote monitoring, calculated in percentage as the ratio between days of transmission and days of follow-up after remote monitoring introduction, and death in patients with a pacemaker are limited. Methods and Results: In this single-center retrospective observational study, we investigated 180 patients with a newly implanted pacemaker capable of using a specific remote monitoring system with daily transmission (79.5±8.8 years, men 50.6%). The study endpoint was all-cause death. During the follow-up period (median 2.7 years), 33 all-cause deaths were reported, and the TR was significantly lower in the deceased patients than in the survivors (89.6±9.6% vs. 95.4±7.0%, P<0.001). The area under the receiver-operating characteristic curve for TR to predict all-cause death was 0.72 (95% confidence interval [CI] 0.62-0.81, P<0.001). A TR of 95% had sensitivity of 74.1% and specificity of 63.6% for predicting all-cause death. In the multivariate Cox regression analysis, TR <95% was selected as a predictor of all-cause death (hazard ratio 3.43, 95% CI 1.61-7.27, P=0.001). Conclusions: Low TR is a predictor of all-cause death in patients with a pacemaker. Patients with TR ≥95% may experience a lower incidence of death, and should have a good prognosis.

Ischemic stroke risk during post-discharge phases of heart failure: association of left ventricular concentric geometry.

Despite a higher risk of ischemic stroke in hospitalized patients with acute heart failure (HF), little is known about the risk of ischemic stroke during the post-discharge phases of HF. Here we investigated (1) the ischemic stroke incidence rate during the post-discharge phases among HF patients receiving standard treatments; (2) the association between ischemic stroke incidence and clinical background, including cardiac structure and function. Among 950 patients who required hospitalization for HF (median duration: 19 days) at our institution, where they received standard treatments, we investigated stroke occurrences during the 2-year period following their discharge and retrospectively evaluated their clinical data. Relative wall thickness (RWT) and left ventricular (LV) mass were determined based on echocardiographic measurements and then used to determine LV geometric patterns. During the follow-up period, ischemic stroke occurred in 25 patients (2.6%) after hospital discharge (1.4 per 100 patient-years). The incidence rate of IS tended to be higher in patients with AF than those without AF (1.8 vs. 1.0 per 100 patient-years, respectively). Notably, multivariate analysis revealed a significant association between RWT and ischemic stroke risk (p < 0.05). RWT was associated with ischemic stroke risk in patients with AF or left atrial enlargement, but not in patients without them. These findings suggest that even with standard HF treatments, the risk of ischemic stroke is high in patients with HF. Moreover, LV concentric geometry is a significant risk factor for ischemic stroke in patients with HF, especially in those with left atrial remodeling and/or AF.

Experience of the use of octreotide for refractory gastrointestinal bleeding in a patient with Jarvik2000® left ventricular assist device.

Gastrointestinal bleeding (GIB) is among the major complications affecting implantable continuous-flow left ventricular assist device (iLVAD) recipients and is the major cause of re-hospitalization. GIB in iLVAD recipients is sometimes critical, and controlling bleeding using conventional approaches is difficult. A 35-year-old woman developed refractory GIB from multiple gastric polyps and de novo angiodysplasia after Jarvik2000® iLVAD implantation. Discontinuation of anticoagulation and antiplatelet therapies had little effect on GIB; thus, multiple endoscopic hemostatic therapies were performed. However, bleeding recurred several times, and red blood cell (RBC) transfusion in large volumes was required for progressive anemia. Furthermore, the von Willebrand factor (VWF) multimer analysis revealed loss of the high-molecular weight multimer, which may have resulted from the high-speed rotation of the axial-flow LVAD pump. To supplement VWF, cryoprecipitate was administered, but it was effective for only several days. Finally, the patient was treated with octreotide, a somatostatin analog, on post-operative day 58. After starting octreotide, tarry stool gradually decreased, and progression of anemia slowed down within the first 14 days of treatment; thus, the total RBC transfusion volume was reduced without additional hemostatic interventions, including cryoprecipitate administration. The patient developed mediastinitis on post-operative day 68 and died of sepsis on post-operative day 72. There was no adverse effect associated with octreotide use. Although the observation period was short, octreotide appears to be useful for resolving recurrent GIB after iLVAD implantation and reducing blood transfusions.

Monitoring treatment response to tafamidis by serial native T1 and extracellular volume in transthyretin amyloid cardiomyopathy.

Tafamidis meglumine, a transthyretin (TTR) stabilizer, is effective in delaying the progression of neuropathy in TTR amyloidosis with Val30Met mutations. However, its efficacy in TTR amyloid cardiomyopathy is not fully elucidated. Herein, we report a 73-year-old Japanese man with a diagnosis of TTR amyloid cardiomyopathy with Val30Met mutation treated with tafamidis. To evaluate treatment response, cardiac magnetic resonance imaging was performed before and after 12 months of tafamidis treatment. Native T1, extracellular volume, and left ventricular mass showed no obvious worsening, and findings of other diagnostic studies also supported the efficacy of tafamidis to delay the progression of amyloid cardiomyopathy. Our case suggests that serial native T1 and extracellular volume may be novel non-invasive imaging methods to monitor the treatment response to TTR stabilizers in cardiac amyloidosis and also that tafamidis may be effective in suppressing cardiac progression in TTR amyloid cardiomyopathy with Val30Met mutation.

Non-atherosclerotic spontaneous coronary artery dissection revascularized by intravascular ultrasonography-guided fenestration with cutting balloon angioplasty.

A 46-year-old woman was referred to our hospital due to chest pain. Twelve-lead electrocardiogram revealed ST-segment elevation suggesting acute myocardial infarction. Emergent coronary angiography showed diffuse narrowing and occlusion in the middle to distal left anterior descending artery (LAD). To investigate the cause of occlusion, an intravascular ultrasound (IVUS) examination was performed and we diagnosed spontaneous coronary artery dissection (SCAD) as the cause of occlusion. After a cutting balloon was dilated at the distal LAD, coronary flow recovered. IVUS-guided angioplasty with cutting balloon could be a choice of treatment in SCAD patients who need revascularization.